A chimeric simian-human immunodeficiency virus (SHIV) has been developed that is highly pathogenic in pig-tailed macaques. This virus contains the core of SIVmac and the envelope of HIV-1 and causes a severe CD4+ T cell loss and an AIDS-like disease within six months of inoculation of pig-tailed macaques. The availability of a pathogenic SHIV will be of considerable benefit to the development and testing of anti-HIV-1 drugs and vaccines. Studies have been initiated using two live virus vaccines that were developed by deletions of specific viral genes from the pathogenic SHIV. Animals received the vaccine strain of SHIV either intravenously or orally and were subsequently evaluated to determine if infection had occurred and to document the animals immune response to the viruses. All animals did become infected with the vaccine strains of SHIV and did develop an immunological response. Preliminary findings in one group of vaccinated animals that were recently challenged by intravaginal inoculation of the pathogenic SHIV suggest that some degree of protection has been provided by exposure to the gene-deleted SHIV.